Periadolescent exposure to cannabinoids alters the striatal and hippocampal dopaminergic system in the adult rat brain.

In a previous work, we have shown that chronic administration of the cannabinoid agonist CP 55,940 (CP) during periadolescence increases cocaine self-administration in adult female rats, while it produces no such effect in males (Higuera-Matas et al., 2008). To extend these findings, we have analysed here the brains of the rats used as subjects in this previous work to evaluate the impact of the interaction between CP exposure and cocaine self-administration on dopaminergic parameters. We evaluated the levels of the dopamine transporter (DAT), and the D1- (D1R) and D2-type (D2R) dopaminergic receptors, as well as tyrosine hydroxylase (TH) mRNA in dopaminergic areas of the adult, cocaine self-administered, rat brain that had been chronically exposed to CP or vehicle (VH) during periadolescence. Control groups with CP/VH exposure and no self-administration experience were also included. In adult females, CP administration induced an up-regulation of DAT in the caudate-putamen that was maintained after cocaine self-administration. In males, CP induced an increase in the D1Rs content in the nucleus accumbens shell, which was not evident after cocaine self-administration. CP also reduced the expression of D2Rs in CA1 irrespective of sex. Finally, an increase in D1Rs was observed in the substantia nigra following cocaine self-administration. These findings suggest that a dopaminergic component modulated by cannabinoids may underlie the enhanced cocaine self-administration previously observed in adult female rats.